PROJECT SUMMARY/ABSTRACT The Tissue and Cell Analysis (TCA) Core provides traditional and cutting-edge technologies necessary for morphological analysis of cells, tissues from experimental animals, and human tissues. Dr. Jerrold Turner, M.D., Ph.D., is a subspecialty-trained GI pathologist who is an expert in routine and advanced imaging approaches and data interpretation. The Co-Director, Dr. Vytas Bindokas, Ph.D., has an extensive understanding of the newest imaging technologies and post-acquisition analytical tools. Together, their complementary skill sets provide users with the guidance needed for effective use of available resources. The TCA is closely aligned with the other Cores of the DDRCC, providing members with the capability of tissue and cell analysis of human and experimental samples derived from their services. The importance of services provided by the TCA Core has only increased in recent years as use of animal models and human specimens has grown exponentially. Tools needed to study these include H&E tissue preparations, simple and complex immunohistochemical stains, and more complicated preparations. The TCA Core also provides a longitudinal array of human specimens that have been well-characterized and preserved, anatomic pathology consultation, instruction in all techniques,(including immunohistochemistry), and specialized guidance specifically related to study of gastrointestinal disease. Slide-scanners can create virtual slides that can be viewed using a computer and virtual microscope software. This makes it possible to preserve the samples for viewing over extended periods of time or to share slides electronically, and greatly simplifies photomicroscopy. In order to study the diverse specimen preparations generated by DDRCC members, the TCA Core provides access to advanced imaging technologies, including superresolution microscopy that makes it possible to overcome the diffraction-limited 250 nm resolution of light microscopy by an order of magnitude. Other tools, including widefield deconvolution, laser scanning confocal, and spinning disk confocal microscopy make it possible to perform intravital imaging of cultured cells and genetically modified animals expressing fluorescent- tagged proteins. These are able to provide previously unattainable views of ongoing pathobiology that allow unprecedented insight into disease mechanisms. Further, as computer power has grown, advanced software that simplifies complex morphometry of enormous 5D (x,y,z,t,?) datasets has become available. The TCA Core has invested in these costly programs and makes their use available to DDRCC members at minimal cost. Perhaps most importantly, the TCA Core provides expert assistance and education in the use of the growing array of routine and highly specialized technologies that are available. This is essential, as the pace of advances makes it difficult for most investigators to be comfortable with or appreciate the benefits of these new tools.